The proposed research will utilize a variety of animal models to gain a further understanding of the negative feedback controls that regulate body weight. In one series of experiments, control rats, rats made obese via electrolytic lesions of the ventromedial hypothalamus, rats rendered obese via daily injections of insulin, and rats rendered obese via forced over-feeding will be compared on many behavioral and biochemical parameters with and without the vagus nerves intact. In another series of experiments, the effect of prolonged maintenance at a grossly under- or over-weight level will be assessed upon subsequent body weight regulation. Finally, the role of the cerebrospinal fluid in controlling body weight will be assessed in chronic dogs and/or monkeys. In particular, the normal relation between cerebrospinal fluid and blood parameters will be assessed in a variety of natural situations (e.g., such as during and after a meal), and the effect of artificial manipulation of the contents of the cerebrospinal fluid will be determined upon acute and chronic feeding and body weight maintenance, as well as upon various humoral parameters.